tbuckley/cabot-search huggingface dataset:
Randomized double-blind, placebo-controlled multicenter phase III study of prevention of irinotecan-induced diarrhea by a probiotic mixture containing <i>Bifidobacterium</i>, BB-12 and <i>Lactobacillus rhamnosus</i>, LGG in colorectal cancer patients: The Probio SK 006-Slovak cooperative oncology group trial.
Authors: Michal Mego, Radoslav Danis, Jozef Chovanec, Silvia Jurisova, Branislav Bystricky, Stefan Porsok, Peter Konkolovsky, Vladimir Vaclav, Maria Wagnerova, Marian Stresko, Bibiana Brezinova, Maria Reckova, Dagmar Sutekova, Natalia Pazderova, Maria Novisedlakova, Eva Zomborska, Sona Ciernikova, Daniela Svetlovska, Lubos Drgona
Journal: Journal of Clinical Oncology (2023)

e24109 Background: The incidence of irinotecan-induced diarrhea varies between 60-90%, by which the incidence of severe diarrhea is 20-40%. The objective of this phase III trial was to determine the effectiveness of the probiotic mixture containing Bifidobacterium, BB-12 and Lactobacillus rhamnosus, LGG in the prophylaxis of irinotecan-induced diarrhea in metastatic colorectal cancer patients due to a reduction in the activity of intestinal beta-D-glucuronidase. Methods: From March 2016 to May 2022, a total of 242 patients with colorectal cancer starting a new line of irinotecan-based therapy were registered to the study in 11 cancer centers in Slovakia. Patients were randomized in a ratio 1:1 to probiotic formula vs. placebo that was administered for 6 weeks. Each capsule of Probio-Tec BG-Vcap-6.5 contained 2.7x10 9 colony-forming units (CFU) of 2 lyophilized probiotic strains Bifidobacterium, BB-12 (50%) and Lactobacillus rhamnosus GG, LGG (50%). Results: Administration of probiotics compared to placebo was not associated with a significant reduction of grade 3/4 diarrhea (placebo arm 11.8% vs. probiotic arm 7.9%, p = 0.38). Neither the overall incidence of diarrhea (46.2% vs. 41.2%, p = 0.51) nor the incidence of enterocolitis (3.4% vs. 0.9%, p = 0.37) was different in the placebo vs. probiotic arm. Subgroup analysis revealed that patients with colostomy had higher incidence of any diarrhea and grade 3/4 diarrhea in the placebo arm compared to the probiotic arm (48.5% vs. 22.2%, p = 0.06 and 15.2% vs. 0%, p = 0.06, respectively). Moreover,patients on probiotic arm had significantly better diarrhea-free survival (HR = 0.41, 95%CI 0.18 – 0.95, p = 0.05) and needed less loperamide (p = 0.01) compared to patients on placebo arm. We did not observe any infection caused by probiotic strains used in this study. Conclusions: This study failed to achieve its primary endpoint, and results suggest a lack of benefit of administered probiotic formula for the prevention of irinotecan-induced diarrhea. However, subgroup analysis suggests a possible benefit in patients with colostomy. Clinical trial information: NCT02819960 .
Utilization and dispensing patterns of medical cannabis products in a state with legalized medical cannabis.
Authors: Amanda Leigh Olson, Stephen Yenzen Lai, Sanjay Shete, Kevin Harbison, Jennifer Scheid, Mika Jankowski, Kimberson Cochien Tanco
Journal: Journal of Clinical Oncology (2023)

e18844 Background: The medical uses of cannabis-based products have been proposed to include treatment of pain, various neurological, gastrointestinal and psychological conditions. Cancer patients are some of the highest utilizers of medical cannabis-based products. To understand real world use and impact of cannabis-based products, we analyzed the database from 4 dispensaries of a cannabis company licensed in New York state. We aim to evaluate the dose, average THC/CBD ratios, association of various medical conditions to THC/CBD dose and cost of products to individuals receiving cannabis-based products. Methods: A retrospective analysis of anonymized data was conducted on 422,201 dispensed products from 32,845 unique individuals aged 18 years and older between 1/1/2016 and 12/31/2020. The database included patients age, gender, qualifying medical condition, type of product, medication directions and amount of product dispensed. Results: Median age was 53 years old and 52% were females. Cancer and non-cancer related pain (85%) were the most common medical condition and inhalation (57%) the most common route. Individuals received a median of 6 prescriptions with median cost of $50/product. Average THC:CBD ratios were 28:0.5mg/day and 12:0.25mg/dose. Highest average cost [mean (95% CI): $73 ($71-$75)] and average CBD/dose per product [mean (95% CI):5.89 (5.38-6.40)] were dispensed for neurological conditions. Highest average THC/dose [mean (95% CI): 14.25 (13.36-15.14)] were found as use as alternative products for those with substance use disorders. Table 1 shows the comparison of gender and route to medical condition. Conclusions: More females received medical cannabis prescriptions while males used more products. Pain was the most common reason for medical cannabis prescriptions. Neurological conditions demonstrated highest average cost and CBD/dose and prescriptions for substance use disorder demonstrated highest THC/dose for products dispensed. Products prescribed had more THC as compared to CBD and inhalation was preferred. As cancer patients increasingly utilize medical cannabis products in conjunction with tumor directed and symptom therapy it will be important to have randomized studies to help guide oncologists. [Table: see text]
Clinical characterization of patients with recurrent glioblastoma in trials involving CED and non-CED treatment.
Authors: Lisa G. Ensign, Denis Boisvert, Norman David LaFrance, Jacob Hendershot, Joel Michalek, Andrew J. Brenner, Ruthanna Davi
Journal: Journal of Clinical Oncology (2023)

e18845 Background: Glioblastoma (GBM) is the most common and aggressive of the primary malignant brain tumors in adults. Bevacizumab (beva) remains the only currently approved therapeutic for recurrent GBM (rGBM) patients who progress on prior therapy. Despite advances in care, rGBM has a median expected progression-free survival (PFS) of &lt; 4 months and overall survival (OS) of ~8 months. NCCN guidelines [Version 2.2022], and other oncology medical societies unanimously recommend patients seek treatment by entering a clinical trial. Since the late 1990’s a number of studies have explored the use of convection-enhanced delivery (CED) of drugs, a well-accepted and widely published delivery option for the treatment of rGBM. This analysis compares the demographics, medical history and survival outcome of patients enrolled into recently completed clinical trials with beva monotherapy to those entered into CED studies. Methods: Data for this analysis was sourced from the Medidata Enterprise Data Store (MEDS), comprised of over 28,000 historical clinical trials for de-identified aggregate patient-level analyses and from the study and patient-level data in the CED studies referenced in D’Amico [J Neurooncol 2021]. Aggregate summary statistics comparing beva and CED patients were based on combined study- and patient-level data using weighted (by sample size) means, incidence and overall survival (OS) rates and median of medians. Results: 163 rGBM beva patients were identified from MEDS. The CED cohort included 636 patients from MEDS and studies referenced in D’Amico. Cohort comparisons (beva vs CED) found median age: 56 vs 55 years; Caucasian race: 91% vs 93%; male sex: 68% vs 65%; not Hispanic or Latino ethnicity: 90% vs 94%; median OS: 7.9 vs 8.4 months. Over the last 2 decades there was a 23% increase in patients with ECOG Performance Status = 0 and 25% decrease in tumor area size at study enrollment, whereas there was no clear temporal OS trend. Conclusions: Patient demographics and most tumor attribute variables were similarly distributed between the beva and CED cohorts. While there is some indication that recent CED studies have enrolled healthier patients with smaller tumors; as expected, this does not appear to have translated to a consistent survival benefit.
Evaluating patient adherence and persistence to first-line tyrosine-kinase inhibitors for metastatic renal cell carcinoma.
Authors: Zhaohui Arter, David Joseph Benjamin, Yen Cao, Michael Forsyth, Ranjit Thirumaran, Jorge Farias, Arash Rezazadeh
Journal: Journal of Clinical Oncology (2023)

e18856 Background: Tyrosine kinase inhibitors (TKIs) have been approved in treating advanced renal cell carcinoma (RCC) since 2005. More recently, combination therapy with an immune checkpoint inhibitor (ICI) and a kinase inhibitor (TKI) is considered standard of care in the first-line setting of metastatic RCC. While oral neoplastic therapies such as TKIs promote patient autonomy, these therapies pose unique challenges including ensuring patients take medications as indicated (i.e., adherence) and for the recommended duration (i.e., persistence). Persistence and adherence data from prescription dispensing and refill patterns are important to health care providers, systems, and payers in order to assess and/or optimize the therapeutic goal(s) of anticancer treatment. Therefore, we sought to explore adherence and persistence of first-line TKIs when used in combination with ICIs for treating metastatic RCC. Methods: Adults with metastatic RCC who received at least two prescriptions for FDA-approved TKIs used in combination with ICIs between April 29, 2019 and August 29,2022 were identified at University of California Irvine Medical Center. Adherence was determined by calculating the Medication Possession Ratio (MPR) and the Proportion of Days Covered (PDC). TKI persistence was evaluated using the Kaplan-Meier method. Also evaluated was the average length of therapy. We examined additional dispensing and refill pattern indicators, including the monthly total number of prescriptions filled. Results: A total of 66 individuals and 849 prescriptions were discovered. The mean duration of treatment for all patients was 237 days, and the median duration was 201 days (Table 1). The mean persistence was 303 days, whereas the median persistence was 233 days. Over 180 days, the median MPR was 83%, whereas the median PDC was 72%. The median variable PDC was 86%, while the median variable MPR was 105%. September was historically the month with the lowest prescription counts (16 +/- 2). Conclusions: We observed a significantly longer median duration of oral TKIs therapy (201 days) in an academic medical center than the national average ( &lt; 100 days). This analysis of real-world data reveals that lengthier treatment durations for TKI+ICI combinations are feasible. Further research is warranted to identify possible factors such as clinical monitoring or adverse effect management that may prolong adherence and persistence. [Table: see text]
Real-world healthcare resource utilization amongst non-small cell lung cancer (NSCLC) patients tested with a host immune classifier (HIC).
Authors: Wade Thomas Iams, Kimberly Le, Nicole Princic, Taylor Marlin
Journal: Journal of Clinical Oncology (2023)

e21210 Background: The HIC is a blood-based proteomic test that measures immune response in patients with NSCLC. The test stratifies patients into two groups, HIC-H and HIC-C which helps evaluate patient prognosis and response to treatment. While clinical validity of the HIC test has been published, no real-world studies have described healthcare resource utilization (HCRU) amongst patients who have been tested with the HIC. This claims analysis describes HCRU amongst patients with NSCLC tested with the HIC. Methods: MarketScan Commercial and Medicare Supplemental Databases linked to Biodesix data files of HIC test results were retrospectively queried to identify patients who were age 18 and older on index date (date of HIC testing), underwent a HIC proteomic test, were continuously enrolled in the MarketScan database for the 6-months before index (pre-index period) and one month post-index, and had at least one non-diagnostic medical claim of lung cancer during the pre-index period. Data utilized was between January 1, 2016 to June 30, 2021. HCRU was measured per patient per month (PPPM) during the pre-index and post-index period and compared between HIC-H and HIC-C cohorts. Results: Of the 328 included patients, 260 patients were HIC-H and 68 were HIC-C. On index, 178 patients had non-metastatic lung cancer and 150 patients had metastatic lung cancer. When examining HCRU in all patients prior to the HIC test, significantly more HIC-C patients had an outpatient visit with an oncologist (40% vs 27%, P &lt; 0.05) or a primary care physician (71% vs 56%, P &lt; 0.05). When assessing only patients with metastatic lung cancer prior to index, significantly more HIC-C patients had inpatient admissions (57% vs 37%, P &lt; 0.05) and more outpatient visits with a primary care physician (73% vs 50%, P &lt; 0.05). When examining HCRU in patients after the HIC test, metastatic patients had significantly more prescriptions (4.6 vs 3.6, P &lt; 0.05). Metastatic HIC-H patients also had significantly more visits to the emergency room (64% vs 43%, P &lt; 0.05). Conclusions: Patients who are identified as HIC-C tend to have higher HCRU earlier in their lung cancer diagnosis and treatment course (prior to HIC testing). In the post-index period, metastatic HIC-H patients had higher HCRU with respect to prescriptions and emergency visits. Other post-index HCRU metrics such as primary care utilization and inpatient admissions were similar among HIC-C and HIC-H patients. Earlier identification of HIC-C and HIC-H patients may help identify those most likely to benefit from additional health system navigation support.
Evaluating root causes contributing to real-world disparities in ovarian cancer care: Insights from an implementation science initiative utilizing tethered patient-provider surveys and chart reviews.
Authors: Kelly E. McKinnon, Kathleen N. Moore, Jeffrey D. Carter, Cherilyn Heggen
Journal: Journal of Clinical Oncology (2023)

e18665 Background: Quality ovarian cancer care is significantly impeded by racial disparities in treatment and survival outcomes for black women with ovarian cancer. In this implementation science (IS) initiative, we evaluated root causes for disparities in care among patients with ovarian cancer at 3 diverse health systems and implemented focused action plans to facilitate improved care quality and promote health equity. Methods: Between 11/2020 and 3/2021, we surveyed oncology team members (n = 53) and ovarian cancer patients (N = 41), and performed randomized and retrospective baseline chart audits (N = 100) at 3 health systems to assess current practices, challenges/barriers, and areas for improvement in equitable care of ovarian cancer patients. Providers then participated in audit/feedback (AF) educational sessions and developed and implemented action plans to address identified gaps. Follow-up chart audits measured practice change following the educational initiative. Results: Significant differences were found between Black and non-Black patients in chart documentation patterns and self-reported survey responses. For example, Black patients were significantly less likely to have chart-documented practices of biomarker testing (BRCA testing 47% of Black patients, and 70% on non-Black patients), assessments for treatment-related adverse events and supportive care (40% vs 70%), fertility counseling (4% vs 17%) and shared decision-making (57% vs. 81%). Patient survey and data suggest racial/cultural differences in the emphasis placed on different treatment decision-making factors, as well as differences in the time/extent to which treatment risks and benefits are discussed with patients. Oncology team members participating in AF sessions developed action plans to improve equitable ovarian cancer care, including increasing education and patient counseling, increasing use of patient navigators, and improving documentation. After implementing action plans, follow-up chart audits showed improvement in the provision of patient education, shared decision-making, biomarker testing, and supportive care for both Black and non-Black patients with ovarian cancer. Conclusions: These findings reveal important factors contributing to racial disparities in ovarian cancer outcomes. The identified gaps may inform future IS initiatives and represent key opportunities for improvement in equitable ovarian cancer patient care. Study Sponsor Statement: The study reported in this abstract was funded by an educational grant from AstraZeneca, GlaxoSmithKline, and Merck &amp; Co. Inc., who had no role in the study design, execution, analysis, or reporting.
A pilot trial of autologous tumor infiltrating lymphocytes (lifileucel, LN-144) for patients with asymptomatic melanoma brain metastases.
Authors: Allison Betof Warner, Michael A. Postow, Katherine Panageas, James William Smithy, Adam Jacob Schoenfeld, Jedd D. Wolchok, Alexander Noor Shoushtari
Journal: Journal of Clinical Oncology (2023)

TPS9606 Background: Melanoma brain metastases (MBM) are a leading cause of morbidity and mortality for patients with advanced melanoma. Modern systemic therapies are insufficient at controlling MBM, and median overall survival (OS) for pts with MBM is &lt; 1 year. Adoptive T cell therapy using tumor infiltrating lymphocytes (TIL) has demonstrated efficacy in advanced melanoma. Lifileucel (LN-144), an autologous TIL product, was recently shown to be safe and effective for patient with PD-1 refractory melanoma. Patients with active MBM were excluded from lifileucel trials to date. Methods: This single-center pilot trial (NCT05640193) is enrolling up to 10 pts with asymptomatic MBM from non-uveal melanoma to receive lifileucel. Patients must have ≥1 intracranial lesion measuring 5-30mm visible on MRI to be used as a target lesion for modified (m)RECIST measurement, progression on prior anti-PD-1 therapy (with or without anti-CTLA-4), progression on targeted therapy if BRAF V600E/K-mutated), ECOG PS ≤1, ≥1 resectable lesion(s) (≥1.5 cm), recovered from prior surgery/anticancer treatment-related AEs (grade ≤1). Patients are not eligible if they have symptomatic MBM and/or require corticosteroids of ≥10 mg/day of prednisone or equivalent. Lifileucel is generated from resected tumor in a centralized GMP process. The regimen includes nonmyeloablative lymphodepletion, lifileucel infusion, and a short course of high-dose IL-2. The primary endpoint is feasibility, defined as ≥7/10 patients who undergo tumor harvest receiving lifileucel infusion. Secondary endpoints are safety, feasibility of manufacturing lifileucel in patients with MBM, and brain metastasis response rate (BMRR) per mRECIST 1.1. Exploratory endpoints include overall objective response rate by mRECIST 1.1, best extracranial response rate, intracranial progression-free survival (PFS), overall PFS, OS. Extensive correlative analyses of peripheral blood mononuclear cells, plasma, tumors, and cerebrospinal fluid are planned to better understand MBM growth, treatment resistance, and response of the central nervous system to lifileucel. Clinical trial information: NCT05640193 .
NK cell expansion after primary multimodal treatment to predict progression free survival in inoperable stage III NSCLC.
Authors: Thomas Philipp Hofer, Lukas Käsmann, Alexander Nieto, Carolyn Pelikan, Julian Taugner, Chukwuka Eze, Amanda Tufman, Claus Belka, Farkhad Manapov, Elfriede Noessner
Journal: Journal of Clinical Oncology (2023)

e20584 Background: During multimodal cancer therapy an acute lymphocytopenia occurs, which is associated with poor survival in inoperable stage III NSCLC patients. A prospective analysis of peripheral blood mononuclear cells (PBMCs) during multimodal treatment was performed to assess dynamic changes of leukocyte subpopulations after concurrent chemo-radioimmunotherapy (cCRT) in order to extract biomarkers to predict progression free survival (PFS). Methods: 20 patients (17 male, 3 female), at median age of 65.5 years (range 34 to 79), 11 suffering from adenocarcinoma, 8 squamous cell carcinoma, and 1 undifferentiated NSCLC, were enrolled in the study. They received thoracic radiotherapy (TRT, 2/20, 10%), cCRT (11/20, 55%), or cCRT with checkpoint inhibition (cCRT-ICI, 7/20, 35%), one patient (1/20, 5%) withdrew consent and was excluded from analysis. Patients were grouped into poor ( &lt; 6months), intermediate (≥6 &lt; 12 months), or favorable (≥12 months) PFS. Blood was analyzed via flow cytometry for leukocyte sub-populations at 9 time points. Here, we report on NK cells and focus on the time period starting after end of TRT until 6 months thereafter. The area under curve (AUC) of absolute cell counts for this period was calculated to provide an aggregate measure for the time-course dynamics. Results: NK cell counts were consistently low in all patients at the end of TRT. Patient-individual recovery of cell counts 6 months after RTend (expressed as the AUC) was observed, which was beneficially affected by consolidation ICI (one-tailed t-test, p = 0.031). Retrospective assignment of the AUC values to the PFS groups revealed a positive association of high AUC values with PFS. Patients with longest PFS (≥12 months; 9/19) had higher AUC values compared to patients with intermediate PFS (≥6 &lt; 12 months; 5/19; t-test p = 0.043) or poor PFS ( &lt; 6months; 5/19; p = 0.0018). The difference between AUC values of intermediate and poor PFS groups was also significant (p = 0.039). Conclusions: Patients who responded with early NK cell expansion after TRT, cCRT, or cCRT-ICI had significantly longer PFS compared to those without increase. Longitudinal monitoring of NK cells and calculating the AUC (RTend and 6 months thereafter), which reflects absolute cell counts, is a promising biomarker to predict PFS.
Chemotherapy induced peripheral neuropathy (CIPN) due to paclitaxel versus docetaxel in patients with early-stage breast cancer receiving taxane therapy: SWOG S1714.
Authors: Meghna S. Trivedi, Joseph M. Unger, Dawn L. Hershman, Amy Darke, Daniel Louis Hertz, Thomas Brannagan, Stephanie Smith, Bryan P. Schneider, William Johnson Irvin, Amanda Redden Hathaway, Amy C. Vander Woude, Vinay K. Gudena, Norah Lynn Henry, Michael Jordan Fisch
Journal: Journal of Clinical Oncology (2023)

12003 Background: Paclitaxel (Pac) and docetaxel (Doc) are used to treat early-stage breast cancer (BC). CIPN due to taxane therapy can cause sensory and motor deficits. CIPN symptoms caused by Pac versus Doc are not well described. Methods: SWOG S1714 enrolled patients ≥ 18 years with Stage I-III primary NSCLC, BC, or ovarian cancer starting treatment with a taxane-based regimen. CIPN was assessed by the patient-reported EORTC QLQ-CIPN20 (CIPN-20) and clinician-assessed NCI-CTCAE. Assessments occurred at baseline and 4, 8, 12, and 24 weeks after registration. Increase in CIPN-20 sensory subscale score ≥ 8 points was considered clinically meaningful. Chi-square and Fisher tests were used for baseline comparisons; logistic regression was used for multivariable analyses. Results: Among 1336 enrolled patients, 1106 of eligible patients had a diagnosis of BC, with median age 54.8 y (range 23.9-84.2 y), 99.3% female, and 72.3% White/11.3% Black/4.6% Asian/11.1% Hispanic/Latino. Pac was administered to 615 (55.6%) and Doc to 491(44.3%) patients. Between the Pac and Doc cohorts, there were significant baseline differences in median age, diabetes, and performance status. At 24 weeks, the proportion of patients with ≥8 point increase in CIPN-20 sensory score was lower for Doc (40.5%) vs Pac (50.2%) (odds ratio [OR] 0.64, 95% CI 0.50, 0.82; multivariable adjusted p&lt;.001). At nearly every timepoint through 24 weeks, patients treated with Pac had more sensory and motor neuropathy as measured by both the CIPN-20 and NCI-CTCAE (Table). Conclusions: In this diverse cohort of patients with BC, the frequency of CIPN was higher than expected for both Pac and Doc and more severe in patients receiving Pac. These findings based on CIPN-20 can assist in treatment decision-making about taxane therapy. Long term follow up will better characterize the differences in the trajectory of CIPN between Pac and Doc. Funding: NIH/NCI/NCORP grant UG1CA189974. Clinical trial information: NCT03939481. [Table: see text]